The purpose of this proposal is to characterize immunoglobulins on the surface of lymphocytes and to study their role in the initiation and regulation of the immune response. There are two means by which immunoglobulins appear on the surface of lymphocytes. The first is by endogenous production and transport to the plasma membrane. The second mechanism is via Fc receptors for immunoglobulin on the surface of lymphocytes which bind particular immunoglobulins present in the extracellular fluid. The endogenously produced immunoglobulin acts as an antigen receptor. In the human there is a striking coexistence of IgM and IgD on the surface of individual cells. The mechanism by which these two distinct immunoglobulin classes are synthesized by single lymphocyte and what their possible functional interrelationships are represent one portion of this application. The nature of the Fc receptor and its possible role in regulating the immune response is the second aspect of this proposal. Physical and chemical analysis of Fc receptors from different cell types will be made and the possible role of these receptors in the cell-cell interactions, B cell triggering by antigen, and antigen recognition by T cells will be tested. BIBLIOGRAPHIC REFERENCES: Rabellino, Enrique M., Grey, Howard M., LaForge, Sandra, Pirofsky, Bernard, Kashiwagi, Noburu, and Malley, Arthur: Antigen heterogeneity of human B and T lymphocytes. J. Clin. Invest. 57:390, 1976. (Reprints not received yet). Kubo, Ralph T., Colon, Sonia M., McCalmon, Robert T., and Grey, Howard M.: Some biological properties of beta2-microglobulin and its antibody. Fed. Proc., April, 1976.